BACKGROUND:People living in homelessness or precarious housing experience more health challenges and earlier mortality than the general population. We characterized longitudinal changes in magnetic resonance imaging (MRI) measures of brain atrophy among people living without stable housing, evaluated risk factors associated with longitudinal atrophy, and assessed whether atrophy was associated with mortality. METHODS:Data was collected as part of an ongoing longitudinal observational study of people living without stable housing in Vancouver, Canada. We included 307 participants with two-or-more brain MRI scans over an average of 7.0 years. We evaluated select risk factors for brain atrophy and assessed whether brain atrophy was associated with mortality during the study. RESULTS:Across 307 participants and 1,173 brain MRI scans, alcohol dependence (β = -0.053, 95% confidence interval [CI] -0.075 to -0.032, p < 0.0001) and higher cardiovascular risk scores (β = -0.021, 95% CI -0.029 to -0.012, p < 0.0001) were associated with more rapid brain atrophy over time, and history of moderate or severe traumatic brain injury was associated with more atrophy at baseline (β = -0.27, 95% CI -0.46 to -0.075, p = 0.0075). More brain atrophy at baseline was associated with mortality during the study, adjusting for age, sex, and other comorbidities (Hazard Ratio [HR]Quartile1 = reference; HRQ2 = 2.37, p = 0.035; HRQ3 = 4.01, p = 0.00032; HRQ4 = 4.91, p < 0.0001). CONCLUSIONS AND RELEVANCE:Alcohol dependence, cardiovascular risk, and traumatic brain injury may represent particularly important risk factors for brain atrophy, and brain atrophy is associated with mortality among people living without stable housing. Targeting these modifiable risk factors may improve brain health and functioning outcomes among people living without stable housing.

Aberrant activation of tau kinases (tauK) has been proposed as a major step in tau hyperphosphorylation and misfolding, and subsequent formation of neurofibrillary tangles (NFT) in Alzheimer's disease (AD). However, evidence of tauK hyperactivation in actual AD brains is scarce and inconsistent, and their role in age-related cognitive decline remains undocumented. We evaluated activated/inhibited species of CDK5/p35/p25, GSK3α/β, and ERK1/2 as well as ten tau/phospho-tau (ptau) peptides (mapping Ser202, Thr217, Ser262, Ser305, and Ser404 phospho-residues) by Western blot or selected reaction monitoring proteomics, respectively, in postmortem dorsolateral prefrontal cortex (DLPFC) and hippocampal samples of 150 participants from the Rush Memory and Aging Project (MAP). Regression models and mediation analyses assessed the contributions of these variables to tau phosphorylation, NFT deposition and antemortem cognitive status of MAP participants. Surprisingly, greater p25 and p35 (indices for CDK5 activation) and lower pSer21/9-GSK3α/β (inhibited species) immunodensities were associated with lower ptau peptide amounts. Individuals with higher p25 cortical densities displayed better cognitive outcomes, particularly working memory. Statistical mediation analyses indicated that the beneficial effect of CDK5/p25 on cognition was mediated by lower densities of phospho-Thr217-tau and NFT deposition in DLPFC, and also identified Thr217 and Ser262 as the ptau sites with greatest influence in both NFT accumulation and cognitive impairment. The present data suggest that tau hyperphosphorylation, tangle deposition, and the subsequent cognitive impairment do not rely on aberrant activation of major tauKs. Additionally, novel evidence was provided for the beneficial contribution of cortical CDK5/p25 to the maintenance of working memory.

Fetal alcohol spectrum disorder (FASD) presents significant clinical challenges, with limited pharmacological options. This mixed-methods study examined cannabis use among 116 Canadian adults with FASD via survey and focus groups/interviews. Overall, 93.3

It is well established that there is an elevated overdose risk with benzodiazepine (BZD) use during opioid agonist treatment (OAT). However, further studies regarding other aspects of how BZDs influence OAT are necessary. This review summarizes the literature on concurrent BZD use with medications for opioid use disorder (MOUD) and how they affect treatment retention in OAT. EMBASE (Ovid), PubMed, and Google Scholar database search tools were used to search for studies that examined the effect of concurrent BZD and MOUD on treatment retention in OAT. Studies published up to January 30th, 2024, were included with no restriction applied other than English language. The criteria for included literature were the presence of both BZD and at least one MOUD as a variable and treatment retention or MOUD adherence as an outcome. Fourteen articles met the criteria for review: eleven retrospective studies and three observational studies. Methadone was utilized in seven studies, buprenorphine in five, naltrexone in one, and suboxone (buprenorphine + naloxone) in one study. The included studies indicated that when BZDs are taken as prescribed and for shorter periods in conjunction with OAT, subjects are retained in their MOUD programs just as well as patients who do not take BZDs. Any potential benefits of increased treatment retention must be balanced against potential harmful effects of BZD use, such as drug overdose and addiction. Further studies must be performed to validate the results of treatment retention and to evaluate other factors that might affect OAT.

RATIONALE:Synthetic cathinones (SC), commonly referred to as "bath salts", are stimulants resembling the natural alkaloid cathinone found in the khat plant. These substances have the potential to induce serious health risks such as hallucinations, delusions, paranoia and agitation which can lead to substance-induced psychotic disorders. Despite growing concerns, there is a limited understanding of the association between SC consumption and the devolvement of such psychopathologies.METHODS:We conducted a systematic review to investigate the frequency of substance-induced psychotic disorder (SIPD) and associated conditions in humans following synthetic cathinone consumption. We qualitatively and quantitatively analyzed SC exposure cases.RESULTS:A total of 32 studies were included, with a diverse range of demographics, synthetic cathinone types, and consumption patterns. The proportion of individuals developing psychotic symptoms was reported at 0.380 (Random-effects model, 95% CI 0.289 - 0.475). Additionally, the significant heterogeneity in diagnostic approaches limited our ability to provide a precise estimate of prevalence.CONCLUSIONS:Synthetic cathinone consumption is associated with the risk of developing psychotic symptoms as indicated by the prevalence of hallucinations and/or delusions. Due to the lack of information on classifying factors, particularly duration of symptoms, we are unable to conclude synthetic cathinone-induced psychosis. Further research is warranted to elucidate the underlying mechanism linking synthetic cathinone consumption and psychosis. This review underscores the urgency of addressing the growing health risks posed by synthetic cathinone use. Additionally, it highlights the necessity of proper quantification of psychotic symptoms through scales and reporting of classification criteria to accurately diagnose SIPD.

Persistent pain is a significant healthcare problem with limited treatment options. The high incidence of comorbid chronic pain and depression significantly reduces life quality and complicates the treatment of both conditions. Antidepressants are less effective for pain and depression than for depression alone and they induce severe side effects. Opioids are highly efficacious analgesics, but rapid development of tolerance, dependence, and debilitating side effects limit their efficacy and safe use. Leucine-enkephalin (Leu-ENK), the endogenous delta opioid receptor agonist, controls pain and mood and produces potent analgesia with reduced adverse effects compared to conventional opioids. High proteolytic instability, however, makes Leu-ENK ineffective after systemic administration and limits its clinical usefulness. KK-103, a Leu-ENK prodrug, was developed to overcome these limitations of Leu-ENK via markedly increased plasma stability in mice. We showed rapid and substantially increased systemic adsorption and blood plasma exposure of KK-103 compared to Leu-ENK. We also observed brain uptake of radiolabeled KK-103 after systemic administration, indicating a central effect of KK-103. We then established KK-103's prolonged antinociceptive efficacy in the ramped hot plate and formalin test. In both models, KK-103 produced a comparable dose to the maximum antinociceptive-effect relationship. The pain-alleviating effect of KK-103 primarily resulted from activating the delta opioid receptor after the likely conversion of KK-103 to Leu-ENK in vivo. Finally, KK-103 produced an antidepressant-like activity comparable to the antidepressant desipramine, but with minimal gastrointestinal inhibition and no incidence of sedation.

Background: There is high inter-individual variability in clozapine metabolism due to genetic and non-genetic differences. Patient-specific factors such as smoking, inflammation indicated by elevated C-reactive protein (CRP), and certain concurrent medications have a significant influence on clozapine metabolism. Aim: To assess which patient-specific factors best explain variability in clozapine metabolism estimated by clozapine concentration to dose (C/D) ratios. Methods: A retrospective cohort analysis using electronic medical data was conducted on 172 inpatients at the BC Psychosis Program. Patients with normal renal and liver function were included if they were on clozapine and had at least one steady-state plasma concentration. The degree of influence of each factor on the variability of clozapine metabolism in the entire cohort and subgroups stratified by fluvoxamine use was evaluated using multiple linear regression analysis of C/D ratios. Results: Model fit testing showed that the entire cohort model accounts for 52.7% of C/D ratio variability, while the no fluvoxamine and fluvoxamine models accounted for 40.8% and 43.8%. In the entire cohort ( n = 172), fluvoxamine use explained the highest variance, and C/D ratios were higher by 30.6% on average. The second strongest predictor was elevated CRP > 10 mg/L, and C/D ratios were higher by 22.9% on average. Subsequently, obesity, nonsmoker status, and female sex explained a significant but modest proportion of variance. Among participants on fluvoxamine ( n = 58), only fluvoxamine dose was associated with an increase, and for every 25 mg increase in dose, C/D ratios increased by 5% on average. Conclusion: In a clinical population, this study replicated the relationship between reduced rate of clozapine metabolism and the use of fluvoxamine, elevated CRP, obesity, nonsmoking status, and female sex; and the magnitude of the effects were large enough to be clinically relevant.

Background: Studies have reported positive associations between drug-induced movement disorders (DIMDs) and symptoms of psychosis in patients with schizophrenia. However, it is not clear which subtypes of symptoms are related to each other, and whether one symptom precedes another. The current report assessed both concurrent and temporal associations between DIMDs and symptoms of psychosis in a community-based sample of homeless individuals. Methods: Participants were recruited in Vancouver, Canada. Severity of DIMDs and psychosis was rated annually, allowing for the analysis of concurrent associations between DIMDs and Positive and Negative Syndrome Scale (PANSS) five factors. A brief version of the PANSS was rated monthly using five psychotic symptoms, allowing for the analysis of their temporal associations with DIMDs. Mixed-effects linear and logistic regression models were used to assess the associations. Results: 401 participants were included, mean age of 40.7 years (SD = 11.2) and 77.4% male. DIMDs and symptoms of psychosis were differentially associated with each other, in which the presence of parkinsonism was associated with greater negative symptoms, dyskinesia with disorganized symptoms, and akathisia with excited symptoms. The presence of DIMDs of any type was not associated with depressive symptoms. Regarding temporal associations, preceding delusions and unusual thought content were associated with parkinsonism, whereas dyskinesia was associated with subsequent conceptual disorganization. Conclusions: The current study found significant associations between DIMDs and symptoms of psychosis in individuals living in precarious housing or homelessness. Moreover, there were temporal associations between parkinsonism and psychotic symptoms (delusions or unusual thought content), and the presence of dyskinesia was temporally associated with higher odds of clinically relevant conceptual disorganization.

One of the most important developments in psychopharmacology in the past decade has been the emergence of novel treatments for mood disorders, such as psilocybin for treatment-resistant depression. Psilocybin is most commonly found in different species of mushroom; however, the literature on mushroom and fungus extracts with potential antidepressant activity extends well beyond just psilocybin-containing mushrooms, and includes both psychedelic and non-psychedelic species. In the current review, we systematically review the preclinical literature on mushroom and fungus extracts, and their effects of animal models of depression and tests of antidepressant activity. The PICO structure, PRISMA checklist and the Cochrane Handbook for systematic reviews of intervention were used to guide the search strategy. A scoping search was conducted in electronic databases PubMed, CINAHL, Embase and Web of Science. The literature search identified 50 relevant and suitable published studies. These included 19 different species of mushrooms, as well as seven different species of other fungi. Nearly all studies reported antidepressant-like effects of treatment with extracts. Treatments were most commonly delivered orally, in both acute and chronically administered studies to predominantly male rodents. Multiple animal models of depression were used, the most common being unpredictable chronic mild stress, while the tail suspension test and forced swim test were most frequently used as standalone antidepressant screens. Details on each experiment with mushroom and fungus species are discussed in detail, while an evaluation is provided of the strengths and weaknesses of these studies.

OBJECTIVE:To examine cognitive intraindividual variability (IIV) dispersion as a predictor of everyday functioning and mortality in persons who are homeless or precariously housed. METHOD:Participants were 407 community-dwelling adults, followed for up to 13 years. Neurocognition was assessed at baseline and IIV dispersion was derived using a battery of standardized tests. Functional outcomes (social, physical) were obtained at baseline and last follow-up. Mortality was confirmed with Coroner's reports and hospital records (N  = 103 deaths). Linear regressions were used to predict current social and physical functioning from IIV dispersion. Repeated measures Analysis of Covariance were used to predict long-term change in functioning. Cox regression models examined the relation between IIV dispersion and mortality. Covariates included global cognition (i.e. mean-level performance), age, education, and physical comorbidities. RESULTS:Higher IIV dispersion predicted poorer current physical functioning (B = -0.46 p = .010), while higher global cognition predicted better current (B  = 0.21, p = .015) and change in social functioning over a period of up to 13 years (F  = 4.23, p = .040). Global cognition, but not IIV dispersion, predicted mortality in individuals under 55 years old (HR = 0.50, p = .013). CONCLUSIONS:Our findings suggest that indices of neurocognitive functioning (i.e. IIV dispersion and global cognition) may be differentially related to discrete dimensions of functional outcomes in an at-risk population. IIV dispersion may be a complimentary marker of emergent physical health dysfunction in precariously housed adults and may be best used in conjunction with traditional neuropsychological indices.

Background: Homeless and precariously housed persons exhibit significant memory impairment, but the component processes underlying memory dysfunction have not been explored. We examined the serial position profile (i.e., primacy and recency effects) of verbal memory and its neuroanatomical correlates to identify the nature of memory difficulties in a large cohort of homeless and precariously housed adults. Method: The sample included 227 community-dwelling homeless and precariously housed adults. Serial position scores (primacy, middle, recency) were computed using the Hopkins Verbal Learning Test-Revised. Paired sample t-tests were used to compare percent recall from each word list region. Age-adjusted correlations assessed associations between serial position scores and other cognitive domains (attention, processing speed, executive functioning). Regression analyses were conducted to examine regional brain volumes of interest (hippocampus, entorhinal cortex, dorsolateral prefrontal cortex [DLPFC]) and their differential associations with serial position scores. Results: The serial position profile was characterized by a diminished recency effect in relation to the primacy effect. Serial position scores positively correlated with sustained attention and cognitive control. Larger hippocampal volume was associated with better primacy item recall. DLPFC volume was not associated with serial position recall after adjustment for false discovery rate. There were no associations between regional brain volumes and recency item recall. Conclusion: Our results suggest that commonly reported memory difficulties in homeless and precariously housed adults are likely secondary to a core deficit in executive control due to compromised frontal lobe functioning. These findings have implications for cognitive rehabilitation in this complex and vulnerable group.

Objective: Many individuals living in precarious housing or homelessness have multimorbid illnesses, including substance use, psychiatric, and neurological disorders. Movement disorders (MDs) associated substance use are amongst the poorly studied subtopics of drug-induced MDs. The aim of the present study was, therefore, to determine the proportion affected and severity of different signs of MDs, as well as their associations with substance use in a community-based sample of precariously housed and homeless individuals.Methods: Participants were recruited from an impoverished urban neighborhood and were assessed for substance dependence and self-reported substance use (alcohol, cannabis, cocaine, methamphetamine, nicotine, and opioids), as well as for the severity of signs of MDs (akathisia, dyskinesia, dystonia, and parkinsonism). Adjusted regression models were used to estimate the associations of the severity of signs with the frequency of substance use over the past 4 weeks and with the baseline diagnosis of substance dependence.Results: The proportion of the sample with clinically relevant signs of MDs in any of the four categories was 18.6% (n = 401), and these participants demonstrated lower levels of functioning than those without signs. Of the different types of substance use, only methamphetamine (its frequency of use and dependence) was significantly associated with greater severity of overall signs of MDs. Frequency of methamphetamine use significantly interacted with age and sex, whereby older female participants exhibited the greatest overall severity with increased methamphetamine use. Of the different signs of MDs, methamphetamine use frequency was positively associated with the severity of trunk/limb dyskinesia and hypokinetic parkinsonism. Relative to no use, concurrent use of antipsychotics demonstrated lower severity of trunk/limb dyskinesia and greater severity of hypokinetic parkinsonism with methamphetamine use, and greater severity of dystonia with cocaine use.Conclusions: Our study found a high proportion of MDs in a relatively young sample, and their severity was consistently associated with methamphetamine use, moderated by participant demographics and antipsychotic use. These disabling sequelae represent an important and understudied neurological condition that may affect quality of life and will require further study.

Introduction Street soccer makes the sport accessible to people affected by homelessness or precarious housing. There is overwhelming evidence that exercise improves physical and mental health. In addition, sport facilitates positive peer pressure that leads to beneficial life changes. Method To examine participants’ accounts of the effects of street soccer in a sample of socially disadvantaged players from Western Canada, we collected 73 cross-sectional self-reports of life changes via a questionnaire. The questionnaire included questions on social, mental, and physical health, including substance use. This allowed the calculation of a modified composite harm score. Results Participants reported improved physical (46% of participants) and mental (43% of participants) health, reduced cigarette (50% of smokers), alcohol (45% of users), cannabis (42% of users), and other non-prescribed drug use, increased number of friends (88% of participants), improved housing (60% of participants), increased income (19% of participants), increased community medical supports (40% of participants), and decreased conflicts with police (47% of those with prior recent conflict). Perceived reductions in substance use were supported by significant changes in composite harm score. Conclusion Street soccer appears to promote improved physical, mental, and social health among people affected by homelessness or precarious housing, with reduction in substance use likely to be a key factor. This work builds upon past qualitative research showing the benefits of street soccer and supports future research which may help elucidate the mechanisms by which street soccer has beneficial effects.

Smoking cannabis in medical users is associated with exposure to harmful toxins. It is important to characterize cannabis-use profiles and risk-factors for medical cannabis users who smoke cannabis. 100 members of a medical cannabis dispensary with mental health concerns were interviewed in detail about their cannabis use. Forty seven percent of participants preferred smoking only, 18% preferred vaporizing, 25% preferred both smoking and vaping, and 10% preferred oral ingestion methods. Smokers differed from other users in multiple ways, including a greater preference for THC-dominant chemovars, and more frequent and greater amount of cannabis consumption. Smoking was also associated with greater rates of alcohol use disorder. These results may inform harm-reduction approaches to decrease the number of individuals smoking cannabis and use less harmful methods of medical cannabis ingestion.

Objective: Myofascial tenderness is present in most chronic pelvic pain conditions and causes significant distress to patients. Treatment is challenging and often not curative. Cannabis is often used for self-management of chronic pelvic pain. However, we do not know which concentrations and routes of administration are most acceptable to users. We aimed to investigate patterns and willingness of cannabis product use among both habitual users and non-users with myofascial pelvic pain (MPP), to inform therapeutic development.Study design: We conducted a cross-sectional study of questionnaire responses from female patients with MPP from two tertiary pelvic pain centers. We aimed for a convenience sample of 100 responses with representation from both centers. Inclusion criteria were age over 18 with pelvic floor muscle tenderness on standard gynecologic examination. We collected information on demographics, pelvic pain history, cannabis use status, cannabis use preferences, validated opioid misuse risk assessment, and interest in using gynecologic cannabis products and used descriptive analyses.Results: 77/135 (57 %) questionnaire respondents were cannabis users and 58 (43 %) were non-users. Most users consume cannabis daily, (48.1 %) orally (66.2 %) or by smoking (60.7 %), and rated cannabis as effective at relieving pelvic pain. 37/58 (63.8 %) non-cannabis users responded that they would be willing to use cannabis for pelvic pain. Lack of information and potential adverse effects were the most common reasons for unwillingness to use. Approximately 3 of 4 respondents were willing to try vaginal or vulvar application of cannabis products for pelvic pain.Conclusions: This cross-sectional study describes cannabis use patterns in MPP patients. Topical vulvar and vaginal cannabis products are of strong interest to both cannabis users and non-users and warrant further research.

Antipsychotics are the only therapeutic class indicated in the symptomatic management of psychotic disorders. However, individuals diagnosed with schizophrenia or schizoaffective disorder may not always benefit from these first-line agents. This refractoriness to conventional treatment can be difficult to address in most clinical settings. Therefore, a referral to a tertiary-care program that is better able to deliver specialized care in excess of the needs of most individuals may be necessary. The average outcome following a period of treatment at these programs tends to be one of improvement. Nonetheless, accurate prognostication of individual-level responses may be useful in identifying those who are unlikely to improve despite receiving specialized care. Thus, the main objective of this study was to predict symptom severity around the time of discharge from the Refractory Psychosis Program in British Columbia, Canada using only clinicodemographic information and prescription drug data available at the time of admission. To this end, a different boosted beta regression model was trained to predict the total score on each of the five factors of the Positive and Negative Syndrome Scale (PANSS) using a data set composed of 320 hospital admissions. Internal validation of these prediction models was then accomplished by nested cross-validation. Insofar as it is possible to make comparisons of model performance across different outcomes, the correlation between predictions and observations tended to be higher for the negative and disorganized factors than the positive, excited, and depressed factors on internal validation. Past scores had the greatest effect on the prediction of future scores across all 5 factors. The results of this study serve as a proof of concept for the prediction of symptom severity using this specific approach.